Enhanced translation of leaderless mRNAs under oxidative stress in Escherichia coli

Abstract

The bacterial response to oxidative stress requires the adaptation of the proteome to the hostile environment. It has been reported that oxidative stress induces a strong and global inhibition of both, transcription and translation. Nevertheless, whereas it is well known that transcription of a small group of genes is induced thanks to transcription factors such as OxyR and SoxR, an equivalent mechanism has not been described for translation. Here we report that whereas canonical translation that depends on Shine Dalgarno recognition is inhibited by oxidative stress in Escherichia coli, the translation of leaderless mRNA (lmRNA) is enhanced under such conditions. Both, inhibition of canonical translation and enhancement of lmRNA translation, depend on the production of (p)ppGpp. We propose that such a mechanism would allow bacteria to rapidly adapt their proteome to hostile conditions and is, perhaps, a general strategy to confront strong stressful conditions. Significance statementThe regulation of translation (the production of proteins based on genetic information) is central for the adaptation to environmental changes. In Escherichia coli translation may begin through two alternative pathways. 1.- A canonical initiation that is well understood and is regulated mostly by changes in the accessibility of ribosomes to specific sequences and 2.- Initiation of leaderless mRNAs (lmRNAs) that lack these sequences and for which we do not understand the regulation process. Our results indicate that under oxidative stress, the production of (p)ppGpp in E. coli inhibits canonical translation and simultaneously enhances translation of lmRNAs, showing for the first time a natural condition where lmRNA translation is regulated and a role for (p)ppGpp in this process.